Dual therapy strategies for COPD: The scientific rationale for LAMA & LABA
COPD is a leading cause of death throughout the world. Chronic exposure to inhaled irritants—commonly cigarette smoke—induces an inflammatory response in the lungs that develops into COPD. Despite the variety in clinical subtypes, (bronchitis, emphysema, and frequent exacerbations) there is no difference in GOLD guideline recommendations for therapeutic interventions among groups.
Bronchodilators are the cornerstone of therapy for all patients with COPD. Muscarinic receptor antagonists block the effects of the parasympathetic nervous system. Beta receptor agonists stimulate the receptors on the smooth muscles of the airways. Both mechanisms relax the smooth muscle tone of the respiratory tract and result in dilation of the airways. Each class of medication is commonly used as monotherapy for treatment of COPD. Studies investigating the short acting bronchodilator effects of albuterol and ipratropium in combination have demonstrated improvements in dyspnea, lung function, and use of rescue medication without compromising safety.
Patients currently prescribed a single long-acting bronchodilator who remain symptomatic may benefit from dual therapy with a long acting beta agonist (LABA) and a long acting muscarinic antagonist (LAMA). This combination has the potential to provide added efficacy for treatment of COPD due to complimentary mechanisms. The beneficial synergistic effects of dual therapy may be achieved at lower doses than required for monotherapy, which may reduce associated adverse effects.
There is a growing group of LAMA/LABA combination therapies in development. Investigations into the risks and benefits of LAMA/LABA therapy have demonstrated benefits that include:
o A reduction in dyspnea
o Improved health-related quality of life scores
o Improved lung function, as assessed by FEV1
o Reduced use of rescue medication.
The impact of this therapy on exacerbation frequency has not been fully elucidated, although some studies have shown a trend. Because the baseline rate of exacerbation is low in inclusion groups for studies of LAMA/LABA dual therapy, the studies are not powered to specifically address exacerbation as a study endpoint. The GOLD guidelines recommend the use of inhaled corticosteroids (ICS) in patients who have a history of acute exacerbations. However, studies assessing prescriber adherence to the GOLD guidelines have demonstrated the frequent use of ICS in patients without such a history. Evidence from ILLUMINATE suggests that switching patients without a history of exacerbations from ICS/LABA therapy to LAMA/LABA therapy may improve symptoms. This may allow patients to avoid steroid treatment and its associated adverse effects.
Regarding onset of acute exacerbations, WISDOM demonstrated non-inferiority of dual LAMA/LABA therapy in patients who stepped down from triple therapy (ICS/LAMA/LABA) compared with patients who remained on triple therapy.